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| Description | 425 amino acids; 47.82 kDa protein. Post translational modifications: Phosphorylation enhances DNA binding. Phosphorylation occurs at position 95, 99, 354, 413 (Serine) and 416 (Threonine). Acetylation brings in a negative charge, acting to neutralise the positive charge on the histones and decreases the interaction of the N termini of histones with the negatively charged phosphate groups of DNA. As a consequence, the condensed chromatin is transformed into a more relaxed structure which is associated with greater levels of gene transcription.
The acetylation sites are: at 2 (Alanine), and 119 (Lysine). Isoform: The following isoforms have been identified:
- RBBP7.iApr07
- hPA25320.1 (469 aa)
- hPA25320.2 (425 aa)
- hPA25320.3 (410 aa)
- hPA25320.7 (420 aa)
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| Expression | It is widely expressed. |
| Localisation | Nucleus. |
| Function | This protein is an ubiquitously expressed nuclear protein and it belongs to a highly conserved subfamily of WD-repeat proteins. It is found among several proteins that bind directly to retinoblastoma protein, which regulates cell proliferation. The encoded protein is found in many histone deacetylase complexes, including mSin3 co-repressor complex. It is also present in protein complexes involved in chromatin assembly, which include the type B histone acetyltransferase (HAT) complex, which is required for chromatin assembly following DNA replication; the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression; the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodelling. This protein can interact with BRCA1 tumor-suppressor gene and may have a role in the regulation of cell proliferation and differentiation. |
| Homology | The percent identity below represents identity of RBBP7 over an aligned region in UniGene.
- M. musculus : 100 (percentage identity)
- C. lupus familiaris : 100
- B. taurus : 100
- R. norvegicus : 100
- G.gallus : 96.2
- D. rerio : 94.4 |
| Note | |
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| Entity | Breast cancer |
| Note | RBBP7 (also known as RbAp46) overexpression has shown to inhibit the tumorigenicity of neoplastigenic breast epithelial cells (Li et al., 2003). RBBP7 activates stress-induced apoptosis, the JNK-dependent apoptotic cell death, possibly through upregulation of GADD45 (Growth arrest- and DNA damage-inducible 45). GADD45 binds and activates MAPKKK MTK1/MEK4, the upstream regulator of JNK, triggering JNK-dependent apoptosis. Thus, overexpression of RBBP7 facilitates stress-induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells. |
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| Entity | Leukemia |
| Note | Expression level of RBBP7 in initial acute leukemia has been found to be significantly higher than in chronic myelogenous leukemia. The Wilms tumor suppressor gene (WT1) expression level was also correlated with RBBP7 expression. WT1 encodes a zinc finger transcription factor that regulates transcription of its downstream gene. RBBP7 is a downstream effector of WT1 gene, and acts in a similar manner as WT1 does. It has been seen that high expression of RBBP7 suppresses the tumorigenicity of neoplastic breast epithelial cells but its overexpression possibly may induce leukemia. This phenomenon suggests that the regulatory pathway for RbAp46 gene expression in acute leukemia may be different from that in solid tumor. |
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| Entity | Human embryonic kidney (HEK) 293 cell tumorigenesis |
| Note | High levels of RbAp46 suppress the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells. High level of RbAp46 resulted in G2/M cell population and augmented apoptosis in serum starved cells. It is possible that overexpression of RbAp46 may interfere with normal cell cycle and/or enhance apoptotic cell death which inhibits the transformation of tumor cells. |
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| WT1-mediated pathway of transcriptional regulation and leukemia. |
| Duan WM, Chen ZX. |
| Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2002 Aug;10(4):366-70. (REVIEW) |
| PMID 12513776 |
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| Rb-associated protein 46 (RbAp46) suppresses the tumorigenicity of adenovirus-transformed human embryonic kidney 293 cells. |
| Guan LS, Li GC, Chen CC, Liu LQ, Wang ZY. |
| Int J Cancer. 2001 Aug 1;93(3):333-8. |
| PMID 11433396 |
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| High expression of RbAp46 gene in patients with acute leukemia or chronic myelogenous leukemia in blast crisis. |
| Hu SY, Chen ZX, Gu WY, Cen JN, Zhao Y. |
| Chin Med J (Engl). 2005 Aug 5;118(15):1295-8. |
| PMID 16117885 |
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| Overexpression of RbAp46 facilitates stress-induced apoptosis and suppresses tumorigenicity of neoplastigenic breast epithelial cells. |
| Li GC, Guan LS, Wang ZY. |
| Int J Cancer. 2003 Jul 20;105(6):762-8. |
| PMID 12767060 |
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| Retinoblastoma suppressor associated protein 46 (RbAp46) attenuates the beta-catenin/TCF signaling through up-regulation of GSK-3beta expression. |
| Li GC, Wang ZY. |
| Anticancer Res. 2006 Nov-Dec;26(6B):4511-8. |
| PMID 17201172 |
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| Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas. |
| Tetu B, Popa I, Bairati I, L'Esperance S, Bachvarova M, Plante M, Harel F, Bachvarov D. |
| Mod Pathol. 2008 Aug;21(8):1002-10. Epub 2008 May 23. |
| PMID 18500265 |
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| Aberrant expression of X-linked genes RbAp46, Rsk4, and Cldn2 in breast cancer. |
| Thakur A, Rahman KW, Wu J, Bollig A, Biliran H, Lin X, Nassar H, Grignon DJ, Sarkar FH, Liao JD. |
| Mol Cancer Res. 2007 Feb;5(2):171-81. |
| PMID 17314274 |
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| RbAp46 inhibits estrogen-stimulated progression of neoplastigenic breast epithelial cells. |
| Zhang TF, Yu SQ, Wang ZY. |
| Anticancer Res. 2007 Sep-Oct;27(5A):3205-9. |
| PMID 17970062 |
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| Expressive profile of retinoblastoma-associated protein 46 and its clinical significance in acute leukemias. |
| Zhou JC, Zhang GS. |
| Zhonghua Xue Ye Xue Za Zhi. 2005 Feb;26(2):86-9. |
| PMID 15921624 |
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